A Study of Guselkumab Administered Subcutaneously in Bio-naive Participants With Active Psoriatic Arthritis Axial Disease

Phase 4Active Not RecruitingNCT04929210

Janssen Research & Development, LLC411 enrolled

Overview

The purpose of this study is to evaluate the efficacy of guselkumab treatment in participants with active psoriatic arthritis (PsA) axial disease by assessing reduction in axial symptoms and inflammation.

PsA is a chronic inflammatory musculoskeletal disease that has 6 disease domains, and axial disease represents one of the domains. Guselkumab is a fully human immunoglobulin (Ig) G1 lambda monoclonal antibody (mAb) that by binding to the p19 protein subunit of interleukin (IL)-23, blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23-mediated intracellular signaling, activation, and cytokine production. This study will consist of a screening phase (up to 6 weeks), a treatment phase (up to 48 weeks, including a placebo-controlled period from Week 0 to Week 24 and an active-controlled treatment phase from Week 24 to Week 48), and a safety follow-up phase (up to Week 60). The efficacy assessments will include assessment such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score and the safety assessments will include evaluations of physical examinations, vital signs, electrocardiograms, clinical laboratory tests, and adverse events. The overall duration of the study will be up to 14 months.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

411

Conditions

Arthritis, Psoriatic

Interventions

GuselkumabDRUG

Guselkumab will be administered as subcutaneous injection.

PlaceboDRUG

Matching placebo will be administered as subcutaneous injection.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have a diagnosis of psoriatic arthritis (PsA) for at least 6 months prior to the first administration of study intervention and meet classification criteria for psoriatic arthritis (CASPAR) criteria at screening * Have active PsA as defined by: a) at least 3 swollen joints and at least 3 tender joints at screening and at baseline and b) C-reactive protein (CRP) greater than or equal to (\>=) 0.3 milligram/deciliter (mg/dL) at screening from the central laboratory, and despite previous non-biologic disease modifying antirheumatic drug (DMARD), apremilast, and/or nonsteroidal anti-inflammatory drug (NSAID) therapy * Have magnetic resonance imaging (MRI)-confirmed PsA axial disease (positive MRI spine and/or sacroiliac \[SI\] joints, shown by a Spondyloarthritis Research Consortium of Canada \[SPARCC\] score of \>= 3 in either the spine or the sacroiliac joints) * Have a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of at least 4, and have a spinal pain score (on a visual analog scale \[VAS\]) of at least 4 * Have active plaque psoriasis, with at least 1 psoriatic plaque of \>= 2 centimeter (cm) diameter and/or nail changes consistent with psoriasis, or documented history of plaque psoriasis Exclusion Criteria: * Has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients * Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to rheumatoid arthritis (RA), ankylosing spondylitis (AS)/non-radiographic-axial spondyloarthritis (this does not include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus, or Lyme disease * Has previously received any biologic treatment * Has ever received a Janus kinase (JAK) inhibitor including but not limited to tofacitinib, baricitinib, filgotinib, peficitinib, decernotinib, upadacitinib or any other investigational JAK inhibitor * Has received any systemic immunosuppressants (example, azathioprine, cyclosporine, 6 thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus) within 4 weeks of the first administration of study intervention

Locations (242)

Outcomes

Primary Outcomes

Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score at Week 24

BASDAI is a self-assessment tool that consists of 6 questions relating to 5 major symptoms of ankylosing spondylitis: fatigue, spinal pain, joint pain, enthesitis, qualitative morning stiffness and quantitative morning stiffness. First 5 items were scored on a 10 centimeter (cm) visual analog scale (VAS) ranging from 0 equals to (=) none to 10=very severe. Quantitative morning stiffness was scored on a 10 cm VAS ranging from 0=0 hours to 10=2 or more hours. 2 scores for qualitative and quantitative morning stiffness were averaged, and total BASDAI score was average of the 5 scores of each symptom, ranging from 0 (none) to 10 (very severe). Higher scores indicate greater disease severity.

Time frame: Baseline and Week 24

Secondary Outcomes

Change from Baseline in Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP) at Week 24

The ASDAS-CRP is a composite of 5 disease activity variables with only partial overlap. The 4 self-reported items included in this index are back pain (VAS), duration of morning stiffness, peripheral pain/swelling, and participant global assessment of disease activity; these are combined with the C-reactive protein (CRP) value. Selected cut-offs for improvement scores are: a change greater than or equal to (\>=) 1.1 units for "clinically important improvement" and a change \>= 2.0 units for "major improvement.

Time frame: Baseline and Week 24

Change from Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 24

DAPSA assessed the joint domain of psoriatic arthritis (PsA) and was derived from the sum of the following components: tender joint count (0-68), swollen joint count (0-66), CRP level (milligram/deciliter \[mg/dL\], value less than \[\<\] lower limit of quantification \[LLOQ\] is considered equal to half of the value of LLOQ for numerical calculations), participant assessment of pain (0-10 cm VAS, 0=no pain, 10=worst possible pain), and participant's global assessment of disease activity on arthritis (0 to 10 cm VAS, 0=excellent and 10=poor). A higher score indicates more active disease activity. Negative changes from baseline indicate improvement of PsA disease activity. The assessment does not have a score range with an upper or lower bound.

Data from ClinicalTrials.gov

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Arizona Arthritis and Rheumatology Research PLLC 1

Avondale, Arizona, United States

Arizona Arthritis & Rheumatology Research, PLLC

Chandler, Arizona, United States

Arizona Arthritis and Rheumatology Research PLLC

Mesa, Arizona, United States

Arizona Arthritis Research, PLC.

Phoenix, Arizona, United States

Arizona Arthritis and Rheumatology Associates

Sun City, Arizona, United States

Southern Arizona VA Healthcare System

Tucson, Arizona, United States

Unity Health-White County Medical Center

Searcy, Arkansas, United States

Kaiser Permanent Medical Center

Fontana, California, United States

Newport Huntington Medical Group

Huntington Beach, California, United States

University Of California San Diego

La Jolla, California, United States

...and 232 more locations

Time frame: Baseline and Week 24

Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 24

HAQ-DI score assess functional status of participant. It is 20 question instrument that assess degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0=indicating no difficulty, to 3=indicating inability to perform a task in that area. Total HAQ score is average of the computed categories scores ranging from 0-3 where 0=least difficulty and 3=extreme difficulty. Lower scores are indicative of better functioning. Negative change from baseline indicates improvement of physical function.

Time frame: Baseline and Week 24

Percentage of Participants with Investigator's Global Assessment (IGA) 0/1 Response at Week 24 among Participants with >= 3% Body Surface Area (BSA) Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline

Percentage of participants with IGA 0/1 response at week 24 among the participants with \>= 3 percent (%) BSA psoriatic involvement and an IGA score of \>= 2 (mild) at baseline will be reported. The IGA documents the investigator's assessment of the participants psoriasis at a given timepoint. Overall lesions are graded for induration, erythema, and scaling using 0 (no evidence), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe) scale. The IGA score of psoriasis is based upon the average of induration, erythema and scaling scores. The participant's psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).

Time frame: Week 24

Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Score for Magnetic Resonance Imaging (MRI) Sacroiliac (SI) Joints at Week 24

Change from baseline in SPARCC score for MRI SI joints at week 24 among the participants with a positive MRI of the sacroiliac joints at baseline will be reported. SPARCC method focuses on the cartilaginous portion of the SI joint, and scores presence (score of 1) versus absence (score of 0) of bone marrow edema in each SI joint quadrant.

Time frame: Baseline and Week 24

Percentage of Participants who Achieve a >= 50 % Improvement from Baseline in BASDAI Score at Week 24

Percentage of participants who achieve a \>= 50 % improvement from baseline in BASDAI score at week 24 will be reported.

Time frame: Baseline and Week 24

Percentage of Participants who Achieve ASDAS Clinically Important Improvement at Week 24

Percentage of participants who achieve ASDAS clinically important improvement at week 24 will be reported.

Time frame: Week 24

Percentage of Participants who Achieve Ankylosing Spondylitis Activity Score (ASAS) 40 Response at Week 24

Percentage of participants who achieve ASAS 40 response at Week 24 will be reported. ASAS 40 defined as improvement from baseline of \>= 40% and with an absolute improvement from baseline of at least 2 on 0 to 10 cm scale in at least 3 of following 4 domains: Participant's global assessment (0 to 10 cm; 0=very well, 10=very poor), total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10 cm; 0=none, 10=very severe); no worsening at all from baseline in remaining domain.

Time frame: Week 24

Percentage of Participants who Achieve ASDAS Major Improvement at Week 24

Percentage of participants who achieve ASDAS major improvement at Week 24 will be reported.

Time frame: Week 24

Change from Baseline in SPARCC Score for MRI Spine at Week 24

Change from baseline in SPARCC score for MRI spine at week 24 among the participants with a positive MRI of the spine at baseline will be reported. The SPARCC scoring system for the spine scores the 6 discovertebral units considered by the reader as the most abnormal, and then separately assesses each quadrant of 3 adjacent sagittal slices, with additional points for "depth" and high "intensity" of the lesion.

Time frame: Baseline and Week 24

Number of Participants with Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Time frame: Up to 60 weeks

Number of Participants with Serious Adverse Events (SAEs)

A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.

Time frame: Up to 60 weeks

Number of Participants with Reasonably Related AEs

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Time frame: Up to 60 weeks

Number of Participants with AEs Leading to Discontinuation of Study Intervention

Number of participants with AEs leading to discontinuation of study intervention will be reported.

Time frame: Up to 60 weeks

Number of Participants with Infections

Number of participants with infections will be reported.

Time frame: Up to 60 weeks

Number of participants with Injection-Site Reactions

Number of participants with injection-site reactions will be reported. A study intervention injection-site reaction is any adverse reaction at a subcutaneous study intervention injection-site.

Time frame: Up to 60 weeks

Number of Participants with Laboratory Abnormalities (Chemistry, Hematology) by Maximum Toxicity (Common Terminology Criteria for Adverse Events [CTCAE 5.0]) Grades

Number of participants with laboratory abnormalities (chemistry, hematology) by maximum toxicity (CTCAE 5.0) grades will be reported. Grade refers to the severity of the AE as follows: Grade 1- Mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2- Moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental Activities of Daily Living (ADL); Grade 3- Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care ADL; Grade 4- Life-threatening consequences, urgent intervention indicated; Grade 5- Death related to AE.

Time frame: Up to 60 weeks

Serum Guselkumab Concentration Over Time

Serum guselkumab concentration over time will be reported.

Time frame: Up to 60 weeks

Number of Participants with Antibodies to Guselkumab

Number of participants with antibodies to guselkumab will be reported.

Time frame: Up to 60 weeks